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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When this study was performed, the OECD guideline for the LLNA did not yet exist.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: approx. 7 weeks old
- Weight at study initiation: 424 - 494 g
- Housing: Group housing of 5 animals
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (1000 mg/kg) (Charles River Breeding and Maintenance Diet for Guinea Pigs, Altromin, Lage, Germany)
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2, 5, 10 and 20 %
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
2, 5, 10 and 20 %
No. of animals per dose:
Experimental group: 10
Control group: 5
Details on study design:
RANGE FINDING TESTS: A preliminary irritation study was conducted in order to select test substance concentrations to be used in the main study. For the induction exposures the highest possible concentration that produced mild to moderate irritation (grades 2 - 3) was used. For challenge exposure the maximum non-irritant concentration was used. Practical feasibility of administration determined the highest starting-concentration for each route. The starting- and subsequent concentrations were taken from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1% and if needed, further lower concentrations using the same steps. For intradermal induction the highest concentration was the maximum concentration that could technically be injected.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 24 and 48 hours
- Site: scapular region
- Frequency of applications: each induction once
- Duration: 2 weeks
- Concentrations: intradermally injected with a 2 % concentration and epidermally exposed to a 50 % concentration.
- Volume: Intradermal injections = 0.1 ml/site; Epidermal application = 0.5 ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Second challenge one week after first challenge
- Exposure period: 24 hours
- Site: contralateral flank
- Concentrations: 50 % test substance concentration
- Evaluation (hr after challenge): 24 and 48 hours after removal of the dressing
Positive control substance(s):
yes
Remarks:
Alpha-Hexylcinnamicaledhyde
Reading:
other: first challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: first challenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
grade 1 reaction (slight)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: grade 1 reaction (slight).
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: first challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
grade 1 reaction (slight)
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: grade 1 reaction (slight).
Reading:
other: first challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
grade 1 reaction (slight)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: grade 1 reaction (slight).
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
grade 1 reaction (slight)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: grade 1 reaction (slight).

Since comparable skin reactions were observed in one control animal and based on the inconsistency in results, it was considered that all reactions observed were signs of non-specific irritation.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In order to assess the cutaneous allergenic potential under GLP conditions, the Maximisation-Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline 406 (Notox B.V., 2001). Test substance (purity: 94.8 weight-%) concentrations selected for the main study were based on the results of a preliminary study.

In the main study, ten experimental animals were intradermally injected with a 2 % concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with vehicle alone (water). Approximately 24 hours before the epidermal induction exposure all animals were treated with 10 % SDS.

Two weeks after the epidermal application all animals were challenged with a 50 % test substance concentration and the vehicle. A second challenge was performed one week later with the same test substance concentration and the vehicle.

First Challenge

Skin reactions of grade 1 were observed in one experimental animal in response to the 50 % test substance concentration. No skin reactions were evident in the control animals.

Second challenge

To confirm the results of the first challenge a second challenge was performed one week later. The animals were then treated with a 50 % test substance concentration and vehicle.

Skin reactions of grade 1 were observed in one experimental animal and one control animal in response to the 50 % test substance concentration.

Yellow staining was observed at the test substance treated skin sites, 24 and 48 hours after challenge first and second challenge. This staining did not hamper the scoring of the skin reactions.

Since comparable skin reactions were observed in one control animal and based on the inconsistency in results, it was considered that all reactions observed were signs of non-specific irritation. These results indicate a sensitisation rate of 0 per cent.


Migrated from Short description of key information:
in vivo, Guinea Pig Maximization Test (GPMT), guinea pig: not sensitising (GLP, OECD 406, Notox B.V., 2001)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitisation under Regulation (EC) No. 1272/2008.